This project will address 2 issues that are responsive to RFA-AI-91-06: (1) development of an improved method to diagnose infection of newborns, and (2) determination of why only some offspring from infected mothers are HIV-infected. Their approach for each of these issues stems from 2 discoveries they recently made in adult populations: (1) Early-infected adults still seronegative by the FDA-approved tests actually are not seronegative, but possess anti-HIV antibody recognizing "native"conformational epitopes of gp160 which are destroyed upon denaturation. Their preliminary studies indicate that HIV-infected newborns mount similar IgM and IgA antibody responses which could be used to diagnose infection. (2) Humans possess polymorphic gene(s) that influence CD4 lymphocyte susceptibility to infection by certain HIV-1 isolates. The differential susceptibility between 2 individuals for any given isolate can be as much as 1,000-fold, and it is their hypothesis that part or much of the reason for differential transmission of HIV from mothers to offspring may involve the genetic susceptibility of the infant to the mother's isolate. The specific aims are to 1) determine the frequency of HIV infecting newborns who produce within the first few months of life anti-HIV IgM and/or IgA antibodies not detected by the current FDA-approved serological tests which recognize "native" antibodies above in comparison to other antibody and antigen tests for assessing HIV infection in clinical outcome of infants; (3) determine if genetic susceptibility or resistance of children to mothers' HIV-1 isolates plays a role in determining positive or negative transmission of the virus to the children.